There is a clinical demand for a bone grafting matrix that offers osteoconductive properties equal to autogenous bone and that can be produced in unlimited supply. Although some bone substitutes are available, many consist of materials that have poor physical handling and resorption characteristics that complicate their use and radiographic evaluation.
Similarly, there is no consistently effective commercial product that supports the maintenance of the chondrocyte phenotype of cartilage tissue, despite years of extensive research. Prior strategies to facilitate the repair of damaged cartilage have included the transplantation of existing host cartilage and/or the implantation of prosthetic devices. Limitations of these methods are the availability of donor tissue and the limited lifespan of prosthetic implants. More recently, the ex vivo cultivation of mature chondrocytes on polymeric scaffolds has been used in an attempt to generate cartilage graft material but this has not yet been widely accepted in part because it involves two surgical procedures: one to harvest chondrocytes and the second to implant them after expansion in vitro.
Collagens and glycosaminoglycans are two classes of biomaterials suited for use in bone regeneration. Collagen based matrices have been used in bone grafting. Type I collagen has good cell adhesive properties, in particular, for bone forming osteoblast cells. Collagen has the capacity to serve both as an active or inert scaffold material for growth.
Hyaluronic acid is a natural component of the cartilage extracellular matrix, and it is readily sterilized, is biodegradable and can be produced in a wide range of consistencies and formats. It is generally biocompatable and its resorption characteristics can be controlled by the manipulation of monomers to polymer forms, most commonly through the esterification of the carboxylic groups of the glucuronic acid residues.
Dextran sulfate is a glycosaminoglycan-like polyionic derivative of dextran and has been shown to be useful as a biomaterial and drug for treatment of hyperlipidemia. It is produced by esterification of dextran, a hydrophilic polymer of glucose synthesized by certain strains of bacteria.
Biological glue comprising fibrin has a long history as a tissue adhesive medical device and is believed to be commercially available in Europe (U.S. Pat. No. 5,260,420, issued Nov. 9, 1993). One obstacle that limits its application is the short turn over and residence time which ranges from a few days to a few weeks depending on the site of implantation. The incorporation of collagen fibers into fibrin glue has been reported (Sierra et al., 1993, Trans. Soc. Biomater., vol. 16:257 and U.S. Pat. No. 5,290,552). However, longer coagulation times are required for the collagen/fibrin compositions compared to fibrin alone.
While these materials have been used separately or in combination with other materials, there has been to date no recognition of combinations and methods of making combinations of such materials to form an advantageous matrix for bone, cartilage, and/or soft tissue repair which does not utilize extraneous cross-linking or ionic binding agents. There remains a need for biodegradable, biocompatable matrices which maintain structural integrity and which can be used to repair tissues without resorting to undesirable ex vivo cultivation methods.